The specific aims of this project are to isolate the polymorphic human histocompatibility antigens (the products of the HLA-A, -B, -C and -D/DR genes in the Major Histocompatibility Complex (MHC) and to elucidate their structures. The molecles which will be studied include HLA-A2, -A28, -B27, -B40, -Cw1, -Cw3, -DRw6 and -DRw8. One of these (HLA-B27) has a very strong association with a human disease. Of special importance is the nature of the alloantigenic site(s) in these molecules which are recognized by alloantibodies and various immune cells such as allo or modified self directed cytolytic T cells. The MHC antigens also mediate various other cell-cell interactions in the immune system. The isolated molecules as well as the structural information about them will be employed in studies of the functions of the molecules. In particular, we wish to explore in as much detail as possible the cytolytic T-cell response both to HLA-A, -B and -C antigens and to HLA-DR antigens and to these antigens modified by chemical means or by interaction with viral antigens. Finally, we hope to use the structural information acquired about these molecules to learn more about how membrane proteins are organized and integrated with cell function.